The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus.

Microparticles (MPs) are small membrane-bound vesicles with potent biological activities that can promote the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus (SLE). These particles contain diverse cellular components and are shed from cells during apoptosis or activation. MPs can drive inflammation and autoimmunity by multiple mechanisms reflecting their content of bioactive molecules and ability to engage multiple receptor systems simultaneously. In the rheumatoid joint, particles can stimulate synovitis via their display of cytokines, chemokines, complement and angiogenesis factors. In SLE, particles can serve as an important source of extracellular nuclear molecules to signal 'danger' and form pathogenic immune complexes. Future studies will define the pathways by which particles promote pathogenesis, strategies to block their activity and their utility as biomarkers to assess disease activity and the response to therapy.

Antiparasitic activity of the antimicrobial peptide HbbetaP-1, a member of the beta-haemoglobin peptide family.

A family of antimicrobial peptides (AMPs) derived from the beta-subunit of haemoglobin was recently isolated from channel catfish, Ictalurus punctatus, infected with Ichthyophthirius multifiliis (ich), an important freshwater fish parasite that causes ichthyophthiriosis. We previously discovered that one of these AMPs, HbbetaP-1, had strong cidal activity against ich as well as another ectoparasite, Tetrahymena pyriformis. HbbetaP-1 toxicity was specific, primarily affecting the trophozoite (trophont) stage of ich. Here, we show that HbbetaP-1 acts more rapidly to kill smaller (presumably less mature) trophonts of ich, taking almost twice as long to kill larger trophonts (P < 0.0001). It acts more rapidly than an unrelated AMP, piscidin 1, which is haemolytic and also lethal to ich trophonts. HbbetaP-1 is potently and selectively lethal to the trophont stage of the dinoflagellate ectoparasite, Amyloodinium ocellatum, one of the most important pathogens of warmwater marine fish. HbbetaP-1 has no effect on the fish gill cell line feeder layer (G1B cells) used to propagate Amyloodinium, further suggesting a highly selective action. These findings suggest that HbbetaP-1 or related AMPs might function in protecting marine as well as freshwater fish and that HbbetaP-1 has highly selective activity against specific life stages of important fish ectoparasites.